The initial (1999) application did not include a Cellular Neuroscience Core. Instead, it proposed separate cores in Neuropathology and Neuroscience, with the latter offering expertise in cell culture. The Director of the Neuroscience Core was David Pleasure, M.D., an internationally recognized neurologist with interests in glial biology of the peripheral and central nervous system. Neuropathology initially was headed by John Trojanowski, M.D., Ph.D. and Dr. Lucy Rorke, M.D., distinguished neuropathologists with respective eminence in neurodegenerative diseases and pediatric brain tumors. As user needs evolved, it became apparent that these facilities should be merged into a single Cellular Neuroscience Core. This was accomplished in 1994 with Dr. Pleasure as the Director. He served in this capacity through the renewal of the Center (1999) until 2001, when leadership passed to Dr. Jeffrey Golden, a pediatric neuropathologist with a primary interest in brain development and its disorders. Dr. Golden first joined CHOP in 1997 and immediately became engaged with the MRDDRC, both as a user and as an Associate Director of the Cellular Neuroscience Core. Dr. Pleasure has continued to serve as the Director of the Stokes Research Institute at CHOP. Since its inception (1994) our Core has provided users with a diverse repertoire of state-of-the-art methods for visualization of the distributions of gene products in normal, developing neural cells and in those undergoing various forms of degeneration and regeneration. We have continually and eagerly added new skills, instrumentation and reagents to better serve our users's needs. In 1995, with the generous assistance of the Children's Hospital, we purchased a Leica confocal microscope to which we added inverted microscopy, stagemounted micromanipulators/microinjectors, and a stage-mounted environmental chamber, thus permitting prolonged observation and manipulation of living cells under physiological conditions. In this manner we offered 8-color capacity fluorescent imaging. Our institution paid for the apparatus and we used MRDDRC funding to partially support a technician who worked with Dr. Peter Bannerman, the Director of Confocal Microscopy. Dr. Bannerman became very skillful in the use of this instrument and he made this valuable expertise available to MRDDRC researchers. We made several other notable technological additions to the Core repertoire, including in situ hybridization in both sections and whole embryos. Our general purpose has been not only to make available a technology, but a consultative service that facilitates implementation of the method as well as the interpretation of data. We adhered to this policy when we also added video-enhanced microscopy in order to better support MRDDRC investigators in analyzing intracellular Ca2+ and Na+ as well as the estimate of mitochondrial potential. We were especially gratified that Dr. Douglas Coulter joined the Core upon his coming to CHOP in 1999. Dr. Coulter added to our "armamentarium" his deep experience in electrophysiology and his background in studying the epilepsies. We also welcomed (2003) Dr. Alex Judkins, a pediatric neuropathologist with interests in pediatric brain injury and pediatric brain tumors v atypical teratoid/rhabadoid tumors and primative neuroectodermal tumors in particular. Supported by funds from the Department of Pathology and CHOP, Dr. Judkins oversees the newly equipped histopathology labs tissue microarrayer and laser-capture microscopy systems. These systems, which are now being utilized by center investigators, will also complement services provided by the Molecular Genetics core and the Analytical Neurochemistry cores. Advances in genetics have rapidly accelerated the discovery of genes implicated in the pathogenesis of the developmental disabilities, including several genes that have been identified by members of our MRDDRC. To better appreciate genotype-phenotype relationships, the Cellular Neuroscience Core plans to offer transgenic and mutagenesis services during the next funding period. The goal is to generate animal models for the specific intent to study disorders relevant to the MRDDRC mission. Dr. Golden has overseen the establishment of a core at CHOP to perform these services. The MRDDRC plans to provide consultation and economical access to this new facility. This exciting advance will help investigators to scrutinize the basis of disease in hitherto inaccessible detail. Indeed, we note with satisfaction that MRDDRC users will explore these models not only with the techniques that our Core offers, but with the plethora of methods that are available through the Molecular Genetics and Analytical Neurochemistry and Spectroscopy Cores. As a result of the continued evolution of this core and the investment by the institution in new technologies and the constant upgrading of equipment, the Cellular Neuroscience Core has been able to provide outstanding services to Center users. Over the past 4.5 years we have serviced 25 investigators;contributing to at least 49 publications. The growth of existing services and the addition of new methods ensures that MRDDRC members enjoy ready access to that technological array that has become so essential to all contemporary interdisciplinary research.